1-Hydroxybenzotriazole → Biphenyl-4-carboxylic acid {2-[4-(2-chloro-phenylamino)-piperidin-1-yl]-2-oxo-ethyl}-amide

HRID 1093574Notes

Reaction equation

HRID 1093574 reaction equation
[C:1]1([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:6]=[CH:5][C:4]([C:7]([NH:9][CH2:10][C:11]([OH:13])=O)=[O:8])=[CH:3][CH:2]=1.CCN(C(C)C)C(C)C.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.Cl.Cl.[Cl:53][C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][C:55]=1[NH:60][CH:61]1[CH2:66][CH2:65][NH:64][CH2:63][CH2:62]1>CN(C=O)C.O>[Cl:53][C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][C:55]=1[NH:60][CH:61]1[CH2:66][CH2:65][N:64]([C:11](=[O:13])[CH2:10][NH:9][C:7]([C:4]2[CH:3]=[CH:2][C:1]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)=[CH:6][CH:5]=2)=[O:8])[CH2:63][CH2:62]1

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2629432-((4-Phenylphenyl)formamido)acetic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 66591362HCID 66591362, compound

Product 1

HCID 44235270Biphenyl-4-carboxylic acid {2-[4-(2-chloro-phenylamino)-piperidin-1-yl]-2-oxo-ethyl}-amideYield 48.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of [(biphenyl-4-carbonyl)-amino]-acetic acid (0.134 g, 0.00053 mol) in DMF (2 mL) was added DIPEA (0.185 g, 0.00143 mol), HOBt (0.0646 g, 0.00048 mol) and EDCI.HCl (0.1098 g, 0.00057 mol) at ambient temperature. After 2 minutes (2-chloro-phenyl)-piperidin-4-yl-amine dihydrochloride (0.118 g, 0.00048 mol) was added and the resulting mixture was stirred at the same temperature overnight. The reaction mixture was then diluted with cold water and the resulting precipitate was isolated by filtration. Purification by preparative TLC using 30% ethyl acetate in hexane as eluent afforded 0.105 g (45%) of biphenyl-4-carboxylic acid {2-[4-(2-chloro-phenylamino)-piperidin-1-yl]-2-oxo-ethyl}-amide. LCMS: 448 (M+1)+, 97.78%, 1H NMR (CDCl3): δ 7.94 (d, 2H), 7.74-7.6 (m, 4H), 7.5-7.38 (m, 2H), 7.2-7.1 (m, 1H), 6.75-6.6 (m, 2H), 4.5 (m, 1H), 4.3 (d, 2H), 4.25 (d, 1H), 3.9 (m, 1H), 3.6 (m, 1H), 3.3 (m, 2H), 3.1 (m, 1H), 2.2 (bt, 2H), 1.5 (m, 2H).

Workup

  1. customthe resulting precipitate was isolated by filtration
  2. customPurification by preparative TLC

Sources & evidence

ORD record
ord-144d2f7174e047ada5e5a19c650bacb4
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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